WO2018235524A1 - Micro fluid device - Google Patents

Micro fluid device Download PDF

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Publication number
WO2018235524A1
WO2018235524A1 PCT/JP2018/020171 JP2018020171W WO2018235524A1 WO 2018235524 A1 WO2018235524 A1 WO 2018235524A1 JP 2018020171 W JP2018020171 W JP 2018020171W WO 2018235524 A1 WO2018235524 A1 WO 2018235524A1
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Prior art keywords
branch
flow
channel
flow path
flow passage
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PCT/JP2018/020171
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French (fr)
Japanese (ja)
Inventor
一彦 今村
延彦 乾
正太郎 小原
隆昌 河野
辰典 ▲高▼松
亮馬 石井
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積水化学工業株式会社
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Application filed by 積水化学工業株式会社 filed Critical 積水化学工業株式会社
Priority to US16/617,315 priority Critical patent/US20210121881A1/en
Priority to EP18821343.3A priority patent/EP3644065A4/en
Priority to CN201880031701.8A priority patent/CN110622007B/en
Publication of WO2018235524A1 publication Critical patent/WO2018235524A1/en

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B81MICROSTRUCTURAL TECHNOLOGY
    • B81BMICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B1/00Devices without movable or flexible elements, e.g. microcapillary devices
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N37/00Details not covered by any other group of this subclass
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0621Control of the sequence of chambers filled or emptied
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0848Specific forms of parts of containers
    • B01L2300/0858Side walls
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/08Regulating or influencing the flow resistance
    • B01L2400/084Passive control of flow resistance
    • B01L2400/086Passive control of flow resistance using baffles or other fixed flow obstructions

Definitions

  • the present invention relates to a microfluidic device having an injection-molded body of synthetic resin.
  • Patent Document 1 discloses a structure in which a flow path enlargement portion is provided to rapidly expand the flow channel cross section of the microchannel. It is supposed that the fluid can be stopped by the increase in the resistance to liquid transfer in the flow path enlarged portion.
  • injection moldings of synthetic resin are widely used to achieve miniaturization and cost reduction.
  • synthetic resin injection-molded body it is necessary to make the inner surface of the flow path into a curved shape at the inflection point where the flow path of the flow path expanding part changes rapidly. Otherwise, it will be difficult to remove the injection molded body from the mold.
  • the curvature radius of the curved surface portion causes a difference in the flowability of the fluid. Therefore, for example, in the case where the main flow path is provided with the flow path expanding portion and the branch flow path is provided with the flow path expanding portion, the fluid may not be reliably weighed on the branch flow path side. That is, there is a possibility that the fluid may flow out to the downstream side from the branch flow path as the weighing unit.
  • An object of the present invention is to provide a microfluidic device capable of reliably performing measurement of fluid into a branch flow channel and dispensing of fluid into a plurality of branch flow channels.
  • a microfluidic device is a microfluidic device having an injection molded body made of synthetic resin and provided with a microchannel, wherein the microchannel is a downstream side of a branch portion and a branch portion. And is connected to the main flow path having the first flow path enlargement portion that increases the flow path resistance, and the branch portion of the main flow path, and is provided downstream of the branch portion And the branch flow path having the second flow path expansion portion where the flow path resistance is increased, and the inner surface of the flow path is curved in the first and second flow path expansion portions,
  • the channel width at the start point of the first and second channel expanding parts is x
  • the radius of curvature R when the curved channel inner surface is viewed in plan is R
  • the first and second channel expanding parts In a circular arc of radius R whose end is the start point and the end points of the first and second channel enlargements
  • a plurality of the branch portions are provided, and a plurality of branch flow paths are connected to the plurality of branch portions in a one-to-one relationship, respectively.
  • TB-TE ⁇ 19 is satisfied.
  • the fluid can be reliably dispensed into the plurality of branch channels.
  • connection channel connecting the second channel expansion parts of the plurality of branch channels is further provided.
  • the waste fluid part connected to the first channel enlargement part is further provided.
  • the branch flow channel is connected to the upstream side of the second flow channel expansion section, and the second flow channel expansion section and the branch flow There is further provided a constriction where the flow path is narrower than the rest of the path.
  • a liquid transfer means provided upstream of the main flow path is further provided.
  • a predetermined amount of fluid is reliably weighed in the branch flow channel, or a predetermined amount of fluid is reliably measured in the plurality of branch flow channels. It becomes possible to dispense.
  • FIG. 1 is a perspective view showing the appearance of a microfluidic device according to an embodiment of the present invention.
  • FIG. 2 is a schematic plan view for explaining a microchannel of a microfluidic device according to an embodiment of the present invention.
  • FIG. 3 is a schematic plan view for explaining the channel width x, the radius of curvature R, and the angle ⁇ .
  • FIG. 4 is a schematic cross-sectional view showing a direction in which the flow channel cross section is enlarged.
  • FIG. 1 is a perspective view showing the appearance of a microfluidic device according to an embodiment of the present invention.
  • the microfluidic device 1 has a substrate 2 made of an injection-molded body of synthetic resin.
  • the cover sheet 3 is laminated on the substrate 2, and the base sheet 4 is laminated on the lower surface of the substrate 2.
  • the cover sheet 3 and the base sheet 4 are made of an elastomer or an inorganic synthetic resin.
  • a microchannel is provided in the substrate 2.
  • a micro flow path means the fine flow path which a micro effect arises, at the time of conveyance of a liquid (micro liquid).
  • the liquid is strongly affected by surface tension, and behaves differently from the liquid flowing in a normal large-sized channel.
  • the cross-sectional shape and size of the microchannel are not particularly limited as long as the above-mentioned micro effect occurs.
  • the cross-sectional shape of the microchannel is generally small (including a square) from the viewpoint of reducing channel resistance.
  • the dimension of one side 20 micrometers or more are preferable, 50 micrometers or more are more preferable, and 100 micrometers or more are more preferable.
  • the dimension of the smaller side is preferably 5 mm or less, more preferably 1 mm or less, and still more preferably 500 ⁇ m or less.
  • the diameter is preferably 20 ⁇ m or more, more preferably 50 ⁇ m or more, and still more preferably 100 ⁇ m or more. From the viewpoint of miniaturizing the microfluidic device, the diameter (in the case of an ellipse, the short diameter) is preferably 5 mm or less, more preferably 1 mm or less, and still more preferably 500 ⁇ m or less.
  • the dimension of the smaller side Is preferably 5 ⁇ m or more, more preferably 10 ⁇ m or more, still more preferably 20 ⁇ m or more, preferably 200 ⁇ m or less, and still more preferably 100 ⁇ m or less.
  • the microchannel 11 has a main channel 12.
  • a micro pump 13 as a liquid feeding means is provided on the upstream side of the main flow path 12.
  • the main flow path 12 is provided with a plurality of branch parts 12a to 12c.
  • the first flow path enlarged portion 12d is provided on the downstream side of the portion where the branch portions 12a to 12c are provided.
  • the first flow passage enlarged portion 12 d is a portion where the flow passage cross section of the main flow passage 12 is rapidly expanded.
  • the first flow path expanding portion 12 d determines the liquid transfer resistance of the fluid transported through the main flow path 12.
  • the waste liquid portion 14 is connected to the first flow path expanding portion 12 d.
  • Branching channels 15 to 17 are connected to the branching portions 12a to 12c, respectively.
  • the branch flow channels 15 to 17 have branch flow channel main portions 15a to 17a connected to the branch portions 12a to 12c.
  • flow passage narrowing portions 15b to 17b are connected to downstream ends of the branch flow passage main portions 15a to 17a.
  • Second channel enlarged portions 15c to 17c are connected to downstream end portions of the after-branching channel narrowed portions 15b to 17b.
  • the downstream end portions of the second flow path expanding portions 15 c, 16 c, and 17 c are connected to the connection flow path 18.
  • a bypass flow passage 19 is provided so as to connect the first flow passage enlarged portion 12 d and the connection flow passage 18.
  • the size of the flow passage cross section of the after-branch flow passage narrowing portion 15b, 16b, 17b is the branched flow which is the remaining portion of the second flow passage enlarged portions 15c, 16c, 17c and the branch flow passages 15, 16, 17. It is smaller than the flow passage cross section of the passage body portions 15a, 16a, 17a. Further, the second flow passage enlarged portions 15c, 16c and 17c are portions where the flow passage cross-sections are rapidly expanded, thereby giving a fluid resistance to the fluid in the respective branched flow passages 15, 16 and 17.
  • TB-TE is set to 5 or more, more preferably 19 or more, with respect to the T value represented by the following formula (1).
  • the TB value is a T value in the second flow path expanding portions 15 c, 16 c, 17 c of the branch flow paths 15, 16, 17, and the TE value is a T value in the first flow path expanding portion 12 d of the main flow path 12. It is a value.
  • FIG. 3 is a schematic plan view showing, in an enlarged manner, a portion in which the after-branch channel narrowed portion 15b of the branch channel 15 and the second channel enlarged portion 15c are connected as one representative example.
  • the channel width x in the equation (1) refers to the channel width (in ⁇ m) at the start point 15c1 of the second channel enlarged portion 15c.
  • the flow passage cross section gradually becomes larger.
  • the substrate 2 made of an injection-molded body since the substrate 2 made of an injection-molded body is used, it is necessary that the inner wall of the flow path is curved like the second flow path enlarged portion 15 c in order to perform the injection molding.
  • the radius of curvature when the curved surface portion is viewed in plan is R (unit: ⁇ m).
  • ⁇ (°) is a central angle with respect to the arc Ra of the radius R with the start point 15c1 and the end point 15c2 of the second flow path enlargement part 15c as the end.
  • is 90 °.
  • the cross section of the flow path in the second enlarged flow path portion 15c gradually increases in plan view, but as shown by arrows A and B in FIG. As shown by arrows C and D, the cross section of the flow path is gradually changed in the lateral direction as well.
  • the arc Ra of the radius R has the start point 15 c 1 and the end point 15 c 2 as ends.
  • central angle (theta) with respect to this circular arc Ra is 120 degrees.
  • the central angle ⁇ with respect to the arc Ra is 60 °.
  • a predetermined amount of fluid is weighed in the branch channels 15, 16, 17 by setting the TB-TE to 5 or more, more preferably 19 or more in the microchannel 11. Also, a predetermined amount of fluid can be reliably dispensed into the branch flow channels 15, 16, 17. This will be described based on the following experimental example.
  • a microfluidic device 1 was prepared in which a cover sheet 3 and a base sheet 4 were laminated on a substrate 2 which is an injection-molded body made of a cycloolefin polymer.
  • a microchannel 11 having two branched channels 15 and 16 was provided with various dimensions.
  • Table 1 below shows the design parameters of the flow path enlargement used as the first and second flow path enlargements 12d, 15c, and 16c.
  • T1 to T36 in Table 1 indicate the numbers of the flow path enlargement parts.
  • each of the second channel enlarged portions and the first channel enlarged portion was made to have dimensions indicated by T numbers, and each microfluidic device 1 was manufactured.
  • Table 2 shows the TB value and the TE value together.
  • the TB value of the branch flow channel is 125 since the flow channel enlarged portion of T29 is included.
  • the TE value is 10.2 because it has the flow path enlarged portion of T11. Therefore, TB-TE is 114.8.
  • microfluidic devices 1 of Experimental Examples 1 to 16 different in TB-TE were manufactured.
  • Example 17-32 Next, one microfluidic device was manufactured in the same manner as described above for the branched flow channel. That is, the microfluidic device 1 was manufactured in the same manner as the experimental examples 1 to 16 except that only one branch flow channel 15 was connected to the main flow channel and the branch flow channel 16 was not provided.
  • the TB values of the branched flow channels were the same as in Experimental Examples 1 to 16, respectively, to fabricate the microfluidic device 1 of Experimental Examples 17 to 32.
  • an aqueous solution with a contact angle of 90 ° was fed, and it was confirmed whether or not a 5 ⁇ L amount of fluid could be reliably weighed in one branch channel.
  • O was attached to Table 4 below, and when the weighing was not surely performed, X was added.
  • the fluid that can be used is not particularly limited, but if the fluid has a contact angle in the range of 70 ° to 130 °, the fluid can be reliably weighed or separated according to the present invention as in the above-mentioned Experimental Examples 1 to 32. It has been confirmed that it can be poured.

Abstract

Provided is a micro fluid device which enables a fluid to be dosed reliably into a branch flow passage, and enables a prescribed amount of the fluid to be dispensed reliably into a plurality of branch flow passages. In a micro flow device 11, a micro flow passage 11 includes a main flow passage 12 and branch flow passages 15 to 17. The main flow passage 12 has a first flow passage expanding portion 12d, and the branch flow passages 15 to 17 have second flow passage expanding portions 15c to 17c. With regard to a T value represented by formula (1), a difference (TB-TE) between a TB value, which is the T value for the branch flow passages, and a TE value, which is the T value for the main flow passage, is at least equal to 5. Formula (1): T={1/(x2·R)}·(θ/90) In formula (1), x is a flow passage width at the starting points of the first and second flow passage expanding portions, and R is the radius of curvature of curved surface shaped parts of the first and second flow passage expanding portions. θ represents a central angle with respect to an arc having a radius of curvature R and having the starting point of the corresponding first or second flow passage expanding portion and an end point of the corresponding flow passage expanding portion as end portions.

Description

マイクロ流体デバイスMicrofluidic device
 本発明は、合成樹脂の射出成型体を有するマイクロ流体デバイスに関する。 The present invention relates to a microfluidic device having an injection-molded body of synthetic resin.
 生化学分析などに、マイクロ流体デバイスが種々提案されている。流体を送液し、所定の部分で停止させたりするには、マイクロ流路に送液抵抗が異なる部分を設ける必要がある。下記の特許文献1では、マイクロ流路の流路断面を急激に拡大させる流路拡大部を設けた構造が開示されている。流路拡大部における送液抵抗の増大により、流体を停止させることができるとされている。 Various microfluidic devices have been proposed for biochemical analysis and the like. In order to send the fluid and stop it at a predetermined portion, it is necessary to provide the microchannel with a portion having a different sending resistance. Patent Document 1 below discloses a structure in which a flow path enlargement portion is provided to rapidly expand the flow channel cross section of the microchannel. It is supposed that the fluid can be stopped by the increase in the resistance to liquid transfer in the flow path enlarged portion.
特表2002-527250号公報Japanese Patent Publication No. 2002-527250
 上記マイクロ流体デバイスでは、小型化及び低コスト化を果たすために、合成樹脂の射出成型体が広く用いられている。このような合成樹脂の射出成型体を製造するには、上記流路拡大部の流路が急激に変化する変曲点において、流路内面を曲面状とする必要がある。さもなければ、成型金型から射出成型体を取り出すことが困難となる。 In the above-mentioned microfluidic device, injection moldings of synthetic resin are widely used to achieve miniaturization and cost reduction. In order to manufacture such a synthetic resin injection-molded body, it is necessary to make the inner surface of the flow path into a curved shape at the inflection point where the flow path of the flow path expanding part changes rapidly. Otherwise, it will be difficult to remove the injection molded body from the mold.
 ところが、上記変曲点付近が曲面となった場合、曲面部の曲率半径によって、流体の流れやすさに差が生じる。従って、例えば、主流路に流路拡大部を設け、分岐流路に流路拡大部を設けた場合、分岐流路側に確実に流体を秤取することができないことがあった。すなわち、秤取部としての分岐流路から流体が下流側に流れだすおそれがあった。 However, when the vicinity of the inflection point becomes a curved surface, the curvature radius of the curved surface portion causes a difference in the flowability of the fluid. Therefore, for example, in the case where the main flow path is provided with the flow path expanding portion and the branch flow path is provided with the flow path expanding portion, the fluid may not be reliably weighed on the branch flow path side. That is, there is a possibility that the fluid may flow out to the downstream side from the branch flow path as the weighing unit.
 また、複数の分岐流路に流体を分注する場合においても、各分岐流路に確実に流体を分注することができないおそれがあった。 Further, even in the case of dispensing the fluid into the plurality of branch channels, there is a possibility that the fluid can not be reliably dispensed into each branch channel.
 本発明の目的は、流体の分岐流路への秤取や複数の分岐流路への流体の分注を確実に行なうことを可能とするマイクロ流体デバイスを提供することにある。 An object of the present invention is to provide a microfluidic device capable of reliably performing measurement of fluid into a branch flow channel and dispensing of fluid into a plurality of branch flow channels.
 本発明に係るマイクロ流体デバイスは、合成樹脂からなる射出成型体を有し、マイクロ流路が設けられているマイクロ流体デバイスであって、前記マイクロ流路が、分岐部と、分岐部より下流側に設けられており、流路抵抗を増大させる第1の流路拡大部とを有する主流路と、前記主流路の前記分岐部に接続されており、前記分岐部よりも下流側に設けられており、流路抵抗が高められている第2の流路拡大部を有する分岐流路とを備え、前記第1,第2の流路拡大部において流路内面が曲面状とされており、前記第1,第2の流路拡大部の開始点における流路幅をx、曲面状の前記流路内面を平面視した場合の曲率半径をR、前記第1,第2の流路拡大部の開始点と、前記第1,第2の流路拡大部の終了点とを端部とする半径Rの円弧に対する中心角をθとしたときに、下記の式(1)で示されるT値について、前記分岐流路についてのT値であるTB値と、前記主流路についてのT値であるTE値との差が、TB-TE≧5を満たしている。 A microfluidic device according to the present invention is a microfluidic device having an injection molded body made of synthetic resin and provided with a microchannel, wherein the microchannel is a downstream side of a branch portion and a branch portion. And is connected to the main flow path having the first flow path enlargement portion that increases the flow path resistance, and the branch portion of the main flow path, and is provided downstream of the branch portion And the branch flow path having the second flow path expansion portion where the flow path resistance is increased, and the inner surface of the flow path is curved in the first and second flow path expansion portions, The channel width at the start point of the first and second channel expanding parts is x, the radius of curvature R when the curved channel inner surface is viewed in plan is R, and the first and second channel expanding parts In a circular arc of radius R whose end is the start point and the end points of the first and second channel enlargements Assuming that the central angle to be set is θ, for the T value represented by the following equation (1), the TB value which is the T value for the branch flow channel and the TE value which is the T value for the main flow channel The difference satisfies TB-TE ≧ 5.
 T={1/(x・R)}・(θ/90)……式(1) T = {1 / (x 2 · R)} · (θ / 90) (1)
 本発明に係るマイクロ流体デバイスのある特定の局面では、前記分岐部が複数設けられており、複数の前記分岐部に複数の分岐流路がそれぞれ1対1で接続されており、前記各分岐流路について、TB-TE≧19を満たしている。この場合には、複数の分岐流路に流体を確実に分注することができる。 In a specific aspect of the microfluidic device according to the present invention, a plurality of the branch portions are provided, and a plurality of branch flow paths are connected to the plurality of branch portions in a one-to-one relationship, respectively. For the path, TB-TE ≧ 19 is satisfied. In this case, the fluid can be reliably dispensed into the plurality of branch channels.
 本発明に係るマイクロ流体デバイスの他の特定の局面では、複数の前記分岐流路の前記第2の流路拡大部同士を連結している連結流路がさらに備えられている。 In another particular aspect of the microfluidic device according to the present invention, a connection channel connecting the second channel expansion parts of the plurality of branch channels is further provided.
 本発明に係るマイクロ流体デバイスのさらに他の特定の局面では、前記第1の流路拡大部に接続されている廃液部がさらに備えられている。 According to still another specific aspect of the microfluidic device according to the present invention, the waste fluid part connected to the first channel enlargement part is further provided.
 本発明に係るマイクロ流体デバイスの別の特定の局面では、前記分岐流路に、前記第2の流路拡大部の上流側に連ねられており、前記第2の流路拡大部及び当該分岐流路の残りの部分よりも流路が狭い狭窄部がさらに設けられている。 In another specific aspect of the microfluidic device according to the present invention, the branch flow channel is connected to the upstream side of the second flow channel expansion section, and the second flow channel expansion section and the branch flow There is further provided a constriction where the flow path is narrower than the rest of the path.
 本発明に係るマイクロ流体デバイスのさらに他の特定の局面では、前記主流路の上流側に設けられた送液手段がさらに備えられている。 In still another particular aspect of the microfluidic device according to the present invention, a liquid transfer means provided upstream of the main flow path is further provided.
 本発明に係るマイクロ流体デバイスによれば、射出成型体を有するマイクロ流体デバイスにおいて、分岐流路に所定量の流体を確実に秤取したり、複数の分岐流路に所定量の流体を確実に分注することが可能となる。 According to the microfluidic device according to the present invention, in a microfluidic device having an injection molded body, a predetermined amount of fluid is reliably weighed in the branch flow channel, or a predetermined amount of fluid is reliably measured in the plurality of branch flow channels. It becomes possible to dispense.
図1は、本発明の一実施形態に係るマイクロ流体デバイスの外観を示す斜視図である。FIG. 1 is a perspective view showing the appearance of a microfluidic device according to an embodiment of the present invention. 図2は、本発明の一実施形態に係るマイクロ流体デバイスのマイクロ流路を説明するための模式的平面図である。FIG. 2 is a schematic plan view for explaining a microchannel of a microfluidic device according to an embodiment of the present invention. 図3は、流路幅x、曲率半径R及び角度θを説明するための模式的平面図である。FIG. 3 is a schematic plan view for explaining the channel width x, the radius of curvature R, and the angle θ. 図4は、流路断面を拡大する方向を示す模式的断面図である。FIG. 4 is a schematic cross-sectional view showing a direction in which the flow channel cross section is enlarged. 図5は、角度θ=120°の場合の流路拡大部における曲面状部分を説明するための模式的平面図である。FIG. 5 is a schematic plan view for explaining a curved surface-like portion in the flow passage enlarged portion in the case of the angle θ = 120 °. 図6は、角度θ=60°の場合の流路拡大部における曲面状部分を説明するための模式的平面図である。FIG. 6 is a schematic plan view for describing a curved surface-like portion in the flow passage enlarged portion when the angle θ = 60 °.
 以下、図面を参照しつつ、本発明の具体的な実施形態を説明することにより、本発明を明らかにする。 Hereinafter, the present invention will be clarified by describing specific embodiments of the present invention with reference to the drawings.
 図1は、本発明の一実施形態に係るマイクロ流体デバイスの外観を示す斜視図である。マイクロ流体デバイス1は、合成樹脂の射出成型体からなる基板2を有する。基板2上に、カバーシート3が積層されており、基板2の下面には、ベースシート4が積層されている。カバーシート3及びベースシート4は、エラストマーや無機合成樹脂からなる。基板2内には、マイクロ流路が設けられている。 FIG. 1 is a perspective view showing the appearance of a microfluidic device according to an embodiment of the present invention. The microfluidic device 1 has a substrate 2 made of an injection-molded body of synthetic resin. The cover sheet 3 is laminated on the substrate 2, and the base sheet 4 is laminated on the lower surface of the substrate 2. The cover sheet 3 and the base sheet 4 are made of an elastomer or an inorganic synthetic resin. A microchannel is provided in the substrate 2.
 なお、マイクロ流路とは、液体(マイクロ液体)の搬送に際し、マイクロ効果が生じるような微細な流路をいう。 In addition, a micro flow path means the fine flow path which a micro effect arises, at the time of conveyance of a liquid (micro liquid).
 このようなマイクロ流路では、液体は、表面張力の影響を強く受け、通常の大寸法の流路を流れる液体とは異なる挙動を示す。 In such a microchannel, the liquid is strongly affected by surface tension, and behaves differently from the liquid flowing in a normal large-sized channel.
 マイクロ流路の横断面形状及び大きさは、上記のマイクロ効果が生じる流路であれば特に限定はされない。例えば、マイクロ流路に流体を流す際、ポンプや重力を用いる場合には、流路抵抗を低下させる観点から、マイクロ流路の横断面形状がおおむね長方形(正方形を含む)の場合には、小さい方の辺の寸法で、20μm以上が好ましく、50μm以上がより好ましく、100μm以上がさらに好ましい。マイクロ流体デバイス小型化の観点からは、上記小さい方の辺の寸法で、5mm以下が好ましく、1mm以下がより好ましく、500μm以下がさらにより好ましい。また、マイクロ流路の横断面形状がおおむね円形の場合には、直径(楕円の場合には、短径)が、20μm以上が好ましく、50μm以上がより好ましく、100μm以上がさらに好ましい。マイクロ流体デバイス小型化の観点からは、直径(楕円の場合には、短径)は5mm以下が好ましく、1mm以下がより好ましく、500μm以下がさらにより好ましい。 The cross-sectional shape and size of the microchannel are not particularly limited as long as the above-mentioned micro effect occurs. For example, when using a pump or gravity when flowing a fluid in a microchannel, the cross-sectional shape of the microchannel is generally small (including a square) from the viewpoint of reducing channel resistance. In the dimension of one side, 20 micrometers or more are preferable, 50 micrometers or more are more preferable, and 100 micrometers or more are more preferable. From the viewpoint of miniaturization of the microfluidic device, the dimension of the smaller side is preferably 5 mm or less, more preferably 1 mm or less, and still more preferably 500 μm or less. In the case where the cross-sectional shape of the microchannel is generally circular, the diameter (short diameter in the case of an ellipse) is preferably 20 μm or more, more preferably 50 μm or more, and still more preferably 100 μm or more. From the viewpoint of miniaturizing the microfluidic device, the diameter (in the case of an ellipse, the short diameter) is preferably 5 mm or less, more preferably 1 mm or less, and still more preferably 500 μm or less.
 一方、例えば、マイクロ流路に流体を流す際、毛細管現象を有効に活用する場合には、マイクロ流路の横断面形状がおおむね長方形(正方形を含む)の場合には、小さい方の辺の寸法で5μm以上であることが好ましく、10μm以上であることがより好ましく、20μm以上であることがさらにより好ましく、200μm以下であることが好ましく、100μm以下であることがさらに好ましい。 On the other hand, for example, when using a capillary phenomenon effectively when flowing a fluid in a microchannel, when the cross-sectional shape of the microchannel is substantially rectangular (including a square), the dimension of the smaller side Is preferably 5 μm or more, more preferably 10 μm or more, still more preferably 20 μm or more, preferably 200 μm or less, and still more preferably 100 μm or less.
 図2に示すように、マイクロ流路11は、主流路12を有する。主流路12の上流側に送液手段としてのマイクロポンプ13が設けられている。 As shown in FIG. 2, the microchannel 11 has a main channel 12. On the upstream side of the main flow path 12, a micro pump 13 as a liquid feeding means is provided.
 主流路12には、複数の分岐部12a~12cが設けられている。また、分岐部12a~12cが設けられている部分よりも下流側に第1の流路拡大部12dが設けられている。第1の流路拡大部12dは、主流路12の流路断面が急激に拡大する部分である。この第1の流路拡大部12dにより、主流路12を搬送される流体の送液抵抗が決定されることになる。 The main flow path 12 is provided with a plurality of branch parts 12a to 12c. In addition, the first flow path enlarged portion 12d is provided on the downstream side of the portion where the branch portions 12a to 12c are provided. The first flow passage enlarged portion 12 d is a portion where the flow passage cross section of the main flow passage 12 is rapidly expanded. The first flow path expanding portion 12 d determines the liquid transfer resistance of the fluid transported through the main flow path 12.
 第1の流路拡大部12dには、廃液部14が連ねられている。 The waste liquid portion 14 is connected to the first flow path expanding portion 12 d.
 上記分岐部12a~12cには、それぞれ、分岐流路15~17が接続されている。分岐流路15~17は、分岐部12a~12cに連なる分岐流路本体部15a~17aを有する。分岐流路本体部15a~17aの下流側端部に分岐後流路狭窄部15b~17bが連ねられている。分岐後流路狭窄部15b~17bの下流側端部に、第2の流路拡大部15c~17cが連ねられている。第2の流路拡大部15c,16c,17cの下流側端部が連結流路18に連結されている。また、上記第1の流路拡大部12dと、連結流路18とを結ぶように、バイパス流路19が設けられている。 Branching channels 15 to 17 are connected to the branching portions 12a to 12c, respectively. The branch flow channels 15 to 17 have branch flow channel main portions 15a to 17a connected to the branch portions 12a to 12c. After branching, flow passage narrowing portions 15b to 17b are connected to downstream ends of the branch flow passage main portions 15a to 17a. Second channel enlarged portions 15c to 17c are connected to downstream end portions of the after-branching channel narrowed portions 15b to 17b. The downstream end portions of the second flow path expanding portions 15 c, 16 c, and 17 c are connected to the connection flow path 18. Further, a bypass flow passage 19 is provided so as to connect the first flow passage enlarged portion 12 d and the connection flow passage 18.
 上記分岐後流路狭窄部15b,16b,17bの流路断面の大きさは、第2の流路拡大部15c,16c,17c及び分岐流路15,16,17の残りの部分である分岐流路本体部15a,16a,17aの流路断面よりも小さくされている。また、第2の流路拡大部15c,16c,17cは、流路断面が急激に拡大する部分であり、それによって各分岐流路15,16,17における流体に送液抵抗を与える。 The size of the flow passage cross section of the after-branch flow passage narrowing portion 15b, 16b, 17b is the branched flow which is the remaining portion of the second flow passage enlarged portions 15c, 16c, 17c and the branch flow passages 15, 16, 17. It is smaller than the flow passage cross section of the passage body portions 15a, 16a, 17a. Further, the second flow passage enlarged portions 15c, 16c and 17c are portions where the flow passage cross-sections are rapidly expanded, thereby giving a fluid resistance to the fluid in the respective branched flow passages 15, 16 and 17.
 本実施形態の特徴は、下記の式(1)で示すT値について、TB-TEが、5以上、より好ましくは19以上とされていることにある。なおTB値は、分岐流路15,16,17の第2の流路拡大部15c,16c,17cにおけるT値であり、TE値は、主流路12の第1の流路拡大部12dにおけるT値である。 The feature of this embodiment is that TB-TE is set to 5 or more, more preferably 19 or more, with respect to the T value represented by the following formula (1). The TB value is a T value in the second flow path expanding portions 15 c, 16 c, 17 c of the branch flow paths 15, 16, 17, and the TE value is a T value in the first flow path expanding portion 12 d of the main flow path 12. It is a value.
 T={1/(x・R)}・(θ/90)……式(1) T = {1 / (x 2 · R)} · (θ / 90) (1)
 上記T値を、図3を参照して説明する。図3は、一代表例として分岐流路15の分岐後流路狭窄部15bと、第2の流路拡大部15cとが連なっている部分を拡大して示す模式的平面図である。ここで、式(1)中の流路幅であるxとは、第2の流路拡大部15cの開始点15c1における流路幅(単位はμm)をいう。 The T value will be described with reference to FIG. FIG. 3 is a schematic plan view showing, in an enlarged manner, a portion in which the after-branch channel narrowed portion 15b of the branch channel 15 and the second channel enlarged portion 15c are connected as one representative example. Here, the channel width x in the equation (1) refers to the channel width (in μm) at the start point 15c1 of the second channel enlarged portion 15c.
 第2の流路拡大部15cでは、流路断面が次第に大きくなる。ここで、射出成型体からなる基板2を用いているため、射出成型を行なうには、この第2の流路拡大部15cのように、流路の内壁が曲面状であることが必要である。この第2の流路拡大部15cにおいて、曲面状部分を平面視した場合の曲率半径がR(単位はμm)である。そして、θ(°)は、第2の流路拡大部15cの開始点15c1と、終了点15c2とを端部とする、上記半径Rの円弧Raに対する中心角である。従って、図3では、θは90°である。 In the second flow passage enlarged portion 15c, the flow passage cross section gradually becomes larger. Here, since the substrate 2 made of an injection-molded body is used, it is necessary that the inner wall of the flow path is curved like the second flow path enlarged portion 15 c in order to perform the injection molding. . In the second flow passage enlarged portion 15c, the radius of curvature when the curved surface portion is viewed in plan is R (unit: μm). And, θ (°) is a central angle with respect to the arc Ra of the radius R with the start point 15c1 and the end point 15c2 of the second flow path enlargement part 15c as the end. Thus, in FIG. 3, θ is 90 °.
 なお、流路拡大部では、平面視した際に、第2の流路拡大部15cにおいて流路断面が次第に大きくなっているが、図4に矢印A及びBで示すように上下方向に、さらに矢印C及びDで示すように左右方向にも次第に流路断面が大きくなるように変化している。 In the enlarged flow path portion, the cross section of the flow path in the second enlarged flow path portion 15c gradually increases in plan view, but as shown by arrows A and B in FIG. As shown by arrows C and D, the cross section of the flow path is gradually changed in the lateral direction as well.
 なお、図3では、角度θ=90°であった。図5及び図6に、それぞれ、θ=120°及び60°の場合の第2の流路拡大部15cの曲面状部分を模式的平面図で示す。図5に示すように、半径Rの円弧Raは、開始点15c1と終了点15c2とを端部としている。そして、図5では、この円弧Raに対する中心角θは120°となっている。また図6では、この円弧Raに対する中心角であるθが60°である。 In FIG. 3, the angle θ = 90 °. FIGS. 5 and 6 are schematic plan views showing curved surface-shaped portions of the second channel enlarged portion 15c in the case of θ = 120 ° and 60 °, respectively. As shown in FIG. 5, the arc Ra of the radius R has the start point 15 c 1 and the end point 15 c 2 as ends. And in FIG. 5, central angle (theta) with respect to this circular arc Ra is 120 degrees. Further, in FIG. 6, the central angle θ with respect to the arc Ra is 60 °.
 マイクロ流体デバイス1では、マイクロ流路11において、上記TB-TEが5以上、より好ましくは19以上とされていることにより、分岐流路15,16,17に、所定量の流体を秤取したり、分岐流路15,16,17に所定量の流体を確実に分注することができる。これを、以下の実験例に基づき説明する。 In the microfluidic device 1, a predetermined amount of fluid is weighed in the branch channels 15, 16, 17 by setting the TB-TE to 5 or more, more preferably 19 or more in the microchannel 11. Also, a predetermined amount of fluid can be reliably dispensed into the branch flow channels 15, 16, 17. This will be described based on the following experimental example.
 (実験例1~16)
 シクロオレフィンポリマーからなる射出成型体である基板2に、カバーシート3及びベースシート4を積層したマイクロ流体デバイス1を用意した。このマイクロ流体デバイス1内に2個の分岐流路15,16を有するマイクロ流路11を様々な寸法で設けた。下記の表1は、第1,第2の流路拡大部12d,15c,または16cとして用いられる流路拡大部の設計パラメータを示す。表1のT1~T36は、各流路拡大部の番号を示す。
(Experimental examples 1 to 16)
A microfluidic device 1 was prepared in which a cover sheet 3 and a base sheet 4 were laminated on a substrate 2 which is an injection-molded body made of a cycloolefin polymer. In this microfluidic device 1, a microchannel 11 having two branched channels 15 and 16 was provided with various dimensions. Table 1 below shows the design parameters of the flow path enlargement used as the first and second flow path enlargements 12d, 15c, and 16c. T1 to T36 in Table 1 indicate the numbers of the flow path enlargement parts.
 実験例1~16として、下記の表2に示すように、第2の流路拡大部及び第1の流路拡大部をT番号で示す寸法とし、各マイクロ流体デバイス1を作製した。表2には、TB値及びTE値を併せて示す。 As Experimental Examples 1 to 16, as shown in Table 2 below, each of the second channel enlarged portions and the first channel enlarged portion was made to have dimensions indicated by T numbers, and each microfluidic device 1 was manufactured. Table 2 shows the TB value and the TE value together.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
 表2に示すように、例えば実験例1では、分岐流路のTB値は、T29の流路拡大部を有しているため、125である。他方、実験例1においてTE値は、T11の流路拡大部を有しているため、10.2である。従って、TB-TEは114.8となる。 As shown in Table 2, for example, in the experimental example 1, the TB value of the branch flow channel is 125 since the flow channel enlarged portion of T29 is included. On the other hand, in the experimental example 1, the TE value is 10.2 because it has the flow path enlarged portion of T11. Therefore, TB-TE is 114.8.
 上記のようにして、TB-TEが異なる実験例1~16のマイクロ流体デバイス1を作製した。 As described above, microfluidic devices 1 of Experimental Examples 1 to 16 different in TB-TE were manufactured.
 上記マイクロ流体デバイス1内に、接触角90°の水溶液をマイクロポンプ13を用いて送液した。2個の分岐流路15,16に所定量の流体を分注できた場合は下記の表3に分注時の結果として○を付した。複数の分岐流路15,16に、所定量の流体を確実に分注できなかった場合については、×を付した。 An aqueous solution with a contact angle of 90 ° was fed into the microfluidic device 1 using a micropump 13. When a predetermined amount of fluid could be dispensed into the two branch flow channels 15 and 16, the results of dispensing were circled in Table 3 below. In the case where it was not possible to reliably dispense a predetermined amount of fluid into the plurality of branch flow channels 15 and 16, x was attached.
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
 表3から明らかなように、TB-TEが19以上であれば、分岐流路15,16に確実に流体を分注できることがわかる。 As apparent from Table 3, it can be seen that when TB-TE is 19 or more, the fluid can be reliably dispensed into the branch channels 15 and 16.
 (実験例17~32)
 次に、上記分岐流路が1個のマイクロ流体デバイスを上記と同様にして作製した。すなわち、主流路に1本の分岐流路15のみが接続されており、分岐流路16を有しないことを除いては、上記実験例1~16と同様にしてマイクロ流体デバイス1を作製した。この分岐流路のTB値は、それぞれ実験例1~16と同様にして、実験例17~32のマイクロ流体デバイス1を作製した。そして、実験例1~16と同様に、接触角90°の水溶液を送液し、1つの分岐流路に5μL量の流体が確実に秤取されるか否かを確かめた。この秤取が確実に行なわれた場合には、下記の表4に○を付し、秤取が確実に行なわれなかった場合には、×を付した。
(Experimental example 17-32)
Next, one microfluidic device was manufactured in the same manner as described above for the branched flow channel. That is, the microfluidic device 1 was manufactured in the same manner as the experimental examples 1 to 16 except that only one branch flow channel 15 was connected to the main flow channel and the branch flow channel 16 was not provided. The TB values of the branched flow channels were the same as in Experimental Examples 1 to 16, respectively, to fabricate the microfluidic device 1 of Experimental Examples 17 to 32. Then, in the same manner as in Experimental Examples 1 to 16, an aqueous solution with a contact angle of 90 ° was fed, and it was confirmed whether or not a 5 μL amount of fluid could be reliably weighed in one branch channel. In the case where the weighing was surely performed, O was attached to Table 4 below, and when the weighing was not surely performed, X was added.
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
 表4から明らかなように、TB-TEが5以上であれば、1つの分岐流路に所定量の流体を確実に秤取し得ることがわかる。 As apparent from Table 4, it can be seen that when TB-TE is 5 or more, it is possible to reliably measure a predetermined amount of fluid in one branch flow channel.
 なお、使用し得る流体については特に限定されないが、接触角が70°~130°の範囲の流体であれば、上記実験例1~32と同様に、本発明に従って流体を確実に秤取あるいは分注し得ることが確かめられている。 The fluid that can be used is not particularly limited, but if the fluid has a contact angle in the range of 70 ° to 130 °, the fluid can be reliably weighed or separated according to the present invention as in the above-mentioned Experimental Examples 1 to 32. It has been confirmed that it can be poured.
1…マイクロ流体デバイス
2…基板
3…カバーシート
4…ベースシート
11…マイクロ流路
12…主流路
12a~12c…分岐部
12d…第1の流路拡大部
13…マイクロポンプ
14…廃液部
15~17…分岐流路
15a~17a…分岐流路本体部
15b~17b…分岐後流路狭窄部
15c~17c…第2の流路拡大部
15c1…開始点
15c2…終了点
18…連結流路
19…バイパス流路
DESCRIPTION OF SYMBOLS 1 ... Microfluidic device 2 ... Substrate 3 ... Cover sheet 4 ... Base sheet 11 ... Micro flow path 12 ... Main flow path 12a-12c ... Branching part 12d ... 1st flow path enlargement part 13 ... Micro pump 14 ... Waste liquid part 15 ... 17 Branching Channel 15a to 17a Branching Channel Main Body 15b to 17b After Branching Channel Narrowing Section 15c to 17c Second Channel Expanding Section 15c1 Starting Point 15c2 Ending Point 18 Connecting Channel 19 ... Bypass flow path

Claims (6)

  1.  合成樹脂からなる射出成型体を有し、マイクロ流路が設けられているマイクロ流体デバイスであって、
     前記マイクロ流路が、
     分岐部と、該分岐部より下流側に設けられており、流路抵抗を増大させる第1の流路拡大部とを有する主流路と、
     前記主流路の前記分岐部に接続されており、前記分岐部よりも下流側に設けられており、流路抵抗が高められている第2の流路拡大部を有する分岐流路とを備え、
     前記第1,第2の流路拡大部において流路内面が曲面状とされており、前記第1,第2の流路拡大部の開始点における流路幅をx、曲面状の前記流路内面を平面視した場合の曲率半径をR、前記第1,第2の流路拡大部の開始点と、前記第1,第2の流路拡大部の終了点とを端部とする曲率半径Rの円弧に対する中心角をθとしたときに、下記の式(1)で示されるT値について、前記分岐流路についてのT値であるTB値と、前記主流路についてのT値であるTE値との差が、TB-TE≧5を満たしている、マイクロ流体デバイス。
     T={1/(x・R)}・(θ/90)……式(1)
    A microfluidic device comprising an injection-molded body made of a synthetic resin and provided with a microchannel,
    The microchannel is
    A main flow path having a branch portion and a first flow path enlargement portion provided downstream of the branch portion and increasing flow path resistance;
    A branch flow path having a second flow path enlargement portion connected to the branch portion of the main flow path, provided downstream of the branch portion, and in which the flow path resistance is increased;
    The inner surface of the flow passage is curved in the first and second flow passage expanding portions, and the flow passage width at the start point of the first and second flow passage expanding portions is x, and the curved flow passage The radius of curvature where the radius of curvature when the inner surface is viewed in a plan view is R, and the start point of the first and second channel enlarged portions and the end point of the first and second channel enlarged portions are end portions Assuming that the central angle of the arc with respect to the arc of R is θ, a TB value which is a T value for the branch flow channel and a TE value which is a T value for the main flow channel are obtained for T values shown in the following equation (1) The microfluidic device, wherein the difference from the value satisfies TB−TE ≧ 5.
    T = {1 / (x 2 · R)} · (θ / 90) (1)
  2.  前記分岐部が複数設けられており、複数の前記分岐部に複数の分岐流路がそれぞれ1対1で接続されており、前記各分岐流路について、TB-TE≧19を満たしている、請求項1に記載のマイクロ流体デバイス。 A plurality of the branch portions are provided, a plurality of branch flow channels are respectively connected to the plurality of branch portions in a one-to-one manner, and TB-TE ≧ 19 is satisfied for each of the branch flow channels. The microfluidic device according to Item 1.
  3.  複数の前記分岐流路の前記第2の流路拡大部同士を連結している連結流路をさらに備える、請求項2に記載のマイクロ流体デバイス。 The microfluidic device according to claim 2, further comprising a connection channel connecting the second channel enlargements of the plurality of branch channels.
  4.  前記第1の流路拡大部に接続されている廃液部をさらに備える、請求項1~3のいずれか1項に記載のマイクロ流体デバイス。 The microfluidic device according to any one of claims 1 to 3, further comprising a waste liquid connected to the first flow path widening part.
  5.  前記分岐流路に、前記第2の流路拡大部の上流側に連ねられており、前記第2の流路拡大部及び当該分岐流路の残りの部分よりも流路が狭い狭窄部がさらに設けられている、請求項1~4のいずれか1項に記載のマイクロ流体デバイス。 The branch flow channel is connected to the upstream side of the second flow channel expansion section, and a constriction section whose flow channel is narrower than the second flow channel expansion section and the remaining portion of the branch flow channel is further added. The microfluidic device according to any one of the preceding claims, which is provided.
  6.  前記主流路の上流側に設けられた送液手段をさらに備える、請求項1~5のいずれか1項に記載のマイクロ流体デバイス。 The microfluidic device according to any one of claims 1 to 5, further comprising a liquid feeding means provided upstream of the main flow channel.
PCT/JP2018/020171 2017-06-19 2018-05-25 Micro fluid device WO2018235524A1 (en)

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